Because the currently used anticancer drugs are generally not selective enough to cause total tumor eradication, we often find that the initially successful chemotherapy is followed by recurrence of tumor growth, possibly due to the development of drug resistance. Such expressed or acquired resistance may be the result of differences in cell kinetics; or in the cell's ability to repair drug induced damage; or because of the presence of a number of different clones of cells within the tumor, all having different drug sensitivities. It will be our goal to establish several different human tumor cell lines from a single biopsy specimen (and in a variety of tumors); to characterize their in vitro growth kinetics; to determine differential sensitivities to a specific drug, and cross sensitivities and resistance to other drugs; and to determine the causes of these responses when possible. The preliminary results reported in this proposal and the plans for future experiments illustrate that such studies may suggest useful drug combinations and the time sequence of administration for overcoming these forms of resistance.